This proposal outlines the development of a general technique to improve the clinical efficacy of monoclonal antibodies. Monoclonal antibodies are being used in many clinical applications such as cancer, septic shock and transplantation. A number of clinical indications require the deletion of undesired cell types (e.g. tumor cells). Monoclonal antibodies have the specificity to locate the cell type. We propose to use genetic engineering to improve the effector functional activity (e.g. complement cytotoxicity) of monoclonal antibodies. If successful this will improve the clinical use of monoclonal antibodies by not only raising the efficacy but by possibly increasing safety due to a lowered drug load.